The striatum appears to be the most sensitive brain structure to cocaine-- induced increases in extracellular dopamine (EDA). The frontal cortex was much less responsive with little evidence of a dose-dependent response. Chronic cocaine did not alter DA or DA metabolite levels in response to focal cocaine challenges. Higher DA levels were found in the striatum of cocaine pretreated rats following systemic cocaine challenges. Similar effects were found following chronic amphetamine. Autoradiographic analyses revealed that cocaine diffuses approximately 2 mm from the dialysis membrane following focal applications. GBR 12909 appeared to be effective in partially antagonizing the ability of cocaine to increase EDA. Anesthesia does not appear to alter basal MDA levels nor does it alter the peak effects of amphetamine in terms of DA release. Anesthesia does appear to potentiate the effects of morphine on EDA. Focal applications of ethanol to the striatum and n. accumbens produced a dose dependent increase in EDA which was calcium dependent. A wide variety of structures had increased metabolic activity following a single injection of cocaine including: striatum, lateral septum, frontoparietal motor cortex, globus pallidus, substantia nigra and various pontine reticular nuclei. Decreased activity was seen in the lateral habenula and dorsomedial thalamic n. Following chronic administration, increases in activity were also seen in the ventral pallidum, subthalamic n., superior calliculus and cerebellum. The most striking changes during cocaine seizures were increases in metabolic activity in the n. accumbens, olfactory n. and ventral hippocampus. All non-competitive MDA antagonists produced profound rotational behavior in 6-OHDA lesioned rats but only TCP and PCP enhanced EDA. Increases in metabolic activity were seen only in structures receiving nigrotegmental and nigrotectal input following nigral injections of morphine.